There is increasing evidence that natural killer (NK) cells may play an important role in resistance against growth of tumors in vivo. However, most of the studies on NK cell-mediated cytotoxicity have focused on in vitro studies, and only a limited number of investigations concerning NK cells in vivo antitumor potential have been done. The aim of our studies was to investigate involvement of NK cells in in vivo resistance to murine tumors. Using murine ascitic mammary adenocarcinoma 755 model, we found a correlation between augmentation of NK cell cytotoxicity and resistance to the growth of 755 tumor. Specifically, NK cell inducer of pyrimidinone group, 2-amino-5-iodo-6-phenyl-4 pyrimidinol (AIPP), induced high levels of NK cell activity in peritoneal cavity concomitantly with high resistance of B6D2F1 mice to the growth of 755 tumor, the tumor that grew rapidly in control mice. Additionally, such tumor-protective effect was abrogated when the AIPP-stimulated mice were treated with NK cell-specific antiserum NK.1 but not with T-cell-directed antiserum Thy\1.2. These experiments suggest that NK\cells are involved in resistance to mammary adenocarcinoma 755 and suggest that AIPP may be a useful therapeutic agent. The studies on the mechanism of NK cell augmentation indicate that both NK cell tumor-binding, as well as tumor lytic capacity, was augmented by AIPP and that such augmentation was mediated by regionally induced interferon. (HF)